European Patent Application No. 0595635A1 discloses .alpha.-phosphonosulfonate compounds which inhibit cholesterol biosynthesis, and thus are useful as hypocholesterolemic and antiatherosclerotic agents and have the following structure ##STR2## wherein R.sup.2 is OR.sup.5 or R.sup.5a, R.sup.3 and R.sup.5 are the same or different and are H, alkyl, arylalkyl, aryl, cycloalkyl, a metal ion or other pharmaceutically acceptable cation as defined below, or a prodrug ester;
R.sup.5a is H, alkyl, arylalkyl or aryl; PA1 R.sup.4 is H, alkyl, cycloalkyl, aryl, arylalkyl, metal ion or other pharmaceutically acceptable cation as defined below, or a prodrug ester; PA1 z is H, halogen, lower alkyl or lower alkenyl; PA1 R.sup.1 is a lipophilic group containing at least 7 carbons and is alkyl containing from 7 to 25 carbons in the chain; alkenyl containing from 7 to 25 carbons in the chain and from 1 to 6 double bonds; alkynyl containing from 7 to 25 carbons in the chain and from 1 to 6 triple bonds; mixed alkenyl-alkynyl containing 1 to 5 double bonds and 1 to 5 triple bonds; cycloalkyl; cycloheteroalkyl linked through a carbon on the ring or a heteroatom; aryl; heteroaryl; heteroarylalkyl; cycloalkylalkyl; cycloheteroalkylalkyl; or a group of the structure ##STR3## wherein Ar is aryl (such as phenyl or naphthyl), heteroaryl (5 or 6 membered) and may include one to three additional rings fused to Ar (such as aryl, cycloalkyl, heteroaryl or cycloheteroalkyl) and wherein (CH.sub.2).sub.p contains from 1 to 15 carbons, preferably 2 to 12 carbons, in the chain and may include 0, 1, 2 or 3 double bonds and/or 0, 1, 2 or 3 triple bonds in the normal chain, and may contain an ether or amino function in the chain, and/or may include 0, 1, 2 or 3 substituents as defined below for R.sup.6 ; and R.sup.6, R.sup.7, R.sup.8 and R.sup.8a are the same or different and are H, alkyl containing 1 to 40 carbons, preferably from 3 to 25 carbons, alkoxy containing 1 to 40 carbons, preferably from 3 to 25 carbons, alkenyl containing 2 to 40 carbons, preferably from 3 to 25 carbons, alkenyloxy containing 2 to 40 carbons, preferably from 3 to 25 carbons, alkynyl containing 2 to 40 carbons, preferably from 3 to 25 carbons, alkynyloxy containing 2 to 40 carbons, preferably from 3 to 25 carbons, cycloheteroalkyl, cycloheteroalkylalkyl, heteroaryl, cycloalkyl, cycloalkylalkyl, Ar-alkyl, (such as arylalkyl), ArO (such as aryloxy), Ar-amino (such as arylamino), hydroxy, halogen, nitro, Ar (such as aryl), amino, substituted amino wherein the amino includes 1 or 2 substituents (which are alkyl, alkenyl, aryl or any of the Ar groups mentioned above), thiol, alkylthio, Ar-thio (such as arylthio), alkyl-sulfinyl, Ar-sulfinyl (such as arylsulfinyl), alkylsulfonyl, Ar-sulfonyl (such as arylsulfonyl), carboxy, cyano, alkoxycarbonyl, aminocarbonyl, alkylcarbonyloxy, Ar-carbonyloxy (such as arylcarbonyloxy), Ar-carbonylamino (such as arylcarbonylamino) or alkylcarbonylamino, as well as any of the Ar groups as defined above, and preferably wherein the total number of carbons in the substituted Ar--(CH.sub.2).sub.p -- group exceeds 10 carbons; including pharmaceutically acceptable salts thereof such as alkali metal salts such as lithium, sodium or potassium, alkaline earth metal salts such as calcium or magnesium, as well as zinc or aluminum and other FDA approved cations such as ammonium, choline, diethanolamine, ethylenediamine, and salts of naturally occurring amino acids such as arginine, lysine, alanine and the like. PA1 n is 2 to 6, more preferably 2 or 3, and
The (CH.sub.2).sub.p group may contain 1, 2, 3 or more alkyl, alkoxy, alkenyl, alkynyl, hydroxy and/or halogen substituents as well as any of the substituents defined for R.sup.6.
The term "prodrug esters" as employed in the European Patent Application No. 0595635A1 includes prodrug esters which are known in the art for both phosphorus and carboxylic acids. Examples include the following groups: (1-alkanoyloxy)alkyl such as, ##STR4## wherein R.sup.18, R.sup.19 and R.sup.20 are H, alkyl, aryl or arylalkyl; however R.sup.18 O cannot be HO. Examples of such prodrug esters include ##STR5##
European Patent Application No. 0595635A1 also discloses the preparation of the squalene synthetase inhibitor 3-phenoxy-.alpha.-phosphonobenzenebutanesulfonic acid tripotassium salt, including enantiomers thereof, which has the structure ##STR6##